The tremendous promise of a clinical trial of pig islet xenotransplantation is offset by a potentially devastating public health risk: cross species infection. Recent evidence demonstrates that all pigs contain porcine endogenous retroviruses (PoERV). If xenotransplantation of pig islets activates PoERV replication, there is a real risk of spreading this retrovirus to the human host. Therefore, there is a critical need to determine the risk of human infection. The primary objective of this proposal is to develop a unique small animal model using immunodeficient mouse -> human hematopoietic cell chimeras transplanted with pig islets. Specific Aim #1 is to determine the risk of infecting primary human T and B cells and macrophages with PoERV after pig islet transplantation. Specific Aim #2 is to determine the risk of infecting the cellular elements of the human bone marrow thymic and peripheral lymphoid compartments with PoERV after pig islet transplantation.